Evaluation of the renin–angiotensin system in a congenic renin Dahl salt-sensitive rat

Nicholas DiPaola, John Rapp, Paul Brand, William Beierwaltes, Patricia Metting, Steven Britton
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引用次数: 7

Abstract

When an ∼30 centiMorgan (cM) region of chromosome 13 containing the renin gene from the Dahl salt-resistant rat (R) was introgressed into the Dahl salt-sensitive rat (S), the resulting congenic rat (designated S.R-Ren) had a systolic blood pressure on a 2% (w/w) salt diet that was 24 mmHg lower than that of its S counterpart. Due to the large size of the transferred segment (over 30 million bp), the question remained as to whether or not the renin gene was the cause of the blood-pressure difference between the strains. We evaluated the role of the renin–angiotensin system in S.R-Ren and S rats fed a 0.05% salt diet by examining differences between strains in (1) expression of renin in three tissue types, (2) the blood-pressure response to blockade of both angiotensin-converting enzyme and angiotensin II receptors, and (3) pressure natriuresis. No differences were found in renin levels in plasma, kidney or adrenal gland between strains. The blood-pressure responses to the angiotensin-converting-enzyme inhibitor captopril and to the angiotensin II-receptor blocker saralasin in conscious S and S.R-Ren rats were similar. Furthermore, renal function, evaluated by a pressure-natriuresis index that took into account both the time and the arterial pressure needed to excrete an acute salt load, did not differ between strains. Our findings therefore fail to demonstrate a role for the renin gene in conferring lower blood pressure in the congenic rat and suggest that there is an unknown arterial-pressure-regulating locus in this 30 cM region of chromosome 13.

基因肾素达尔盐敏感大鼠肾素-血管紧张素系统的评价
当含有达尔盐抗性大鼠(R)肾素基因的13号染色体约30厘米(cM)区域渗入达尔盐敏感大鼠(S)时,由此产生的基因大鼠(指定S -R - ren)在2% (w/w)盐饮食下的收缩压比S低24毫米汞柱。由于转移片段的大小较大(超过3000万bp),因此关于肾素基因是否是菌株之间血压差异的原因仍然存在疑问。我们通过检测两种菌株之间肾素-血管紧张素系统在三种组织类型中的表达差异,(2)血管紧张素转换酶和血管紧张素II受体被阻断时的血压反应,以及(3)压力尿钠的差异,来评估喂食0.05%盐的S.R-Ren和S大鼠肾素-血管紧张素系统的作用。各组血浆、肾脏和肾上腺肾素水平均无差异。S和S -r - ren清醒大鼠对血管紧张素转换酶抑制剂卡托普利和血管紧张素ii受体阻滞剂萨拉拉西的血压反应相似。此外,考虑到排泄急性盐负荷所需的时间和动脉压力,通过压力-尿钠指数评估的肾功能在品系之间没有差异。因此,我们的研究结果未能证明肾素基因在遗传大鼠中赋予较低血压的作用,并表明在13号染色体的30 cM区域存在未知的动脉压力调节位点。
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